The bacterium Bartonella henselae causes a variety of disease syndromes including severe systemic life-threatening infections in AIDS patients. The NIH Plan for HIV-Related Research (FY2002) lists objective 2F as "elucidate the pathogenic mechanism of HIV-related opportunistic infections in adults and children." Despite the recognition of B. henselae as an emerging pathogen, very little is known about the novel mechanisms by which this bacterium causes disease. This project targets the most unique aspect of Bartonella pathogenesis (angiogenesis), that is observed primarily in AIDS patients with bacillary angiomatosis (BA) and bacillary peliosis hepatis (BPH). The central hypothesis of this proposal is based on a new model of B. henselae -induced angiogenesis that we have advanced requiring a major role for surface proteins and structures of B. henselae in this process. The following specific aims are proposed to test the hypothesis: 1) determine the role each of the four major surface structures of B. henselae play in interaction with host endothelial cells, 2) examine the ability of B. henselae and each of the four major surface structures of B. henselae to induce production of vascular endothelial growth factor (VEGF), 3) determine if VEGF produced by interaction of B. henselae with other cell types is able to function in a paracrine manner to induce proliferation of human microvascula endothelial cells. In vitro cell culture systems will be utilized for both the induction of VEGF (macrophages, fibroblast! epithelial cells) as well as the proliferation of endothelial cells leading to angiogenesis. The definition of the pathogenic processes utilized by B. henselae will help us better understand why this bacterium causes a mild disease in healthy individuals and severe diseases including BA and BPH in AIDS patients.